15-73984854-C-T

Variant names:

• chr15-73984854-C-T
• NM_004809.5:c.808G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004809.5(STOML1):​c.808G>A​(p.Val270Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STOML1 NM_004809.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

Genes affected

STOML1 (HGNC:14560): (stomatin like 1) Predicted to enable ion channel inhibitor activity. Predicted to be involved in lipid transport. Predicted to act upstream of or within SMAD protein signal transduction; cellular response to leukemia inhibitory factor; and negative regulation of acid-sensing ion channel activity. Predicted to be located in cytoplasmic vesicle. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13755494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOML1	NM_004809.5	c.808G>A	p.Val270Met	missense_variant	Exon 6 of 7	ENST00000541638.6	NP_004800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOML1	ENST00000541638.6	c.808G>A	p.Val270Met	missense_variant	Exon 6 of 7	1	NM_004809.5	ENSP00000442478.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.808G>A (p.V270M) alteration is located in exon 6 (coding exon 6) of the STOML1 gene. This alteration results from a G to A substitution at nucleotide position 808, causing the valine (V) at amino acid position 270 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T;.;.;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Benign	1.0	L;.;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.41	.;N;N;.;N
REVEL	Benign	0.25
Sift	Benign	0.11	.;T;T;.;T
Sift4G	Uncertain	0.029	D;D;D;D;D
Polyphen		0.044	B;.;B;.;.
Vest4		0.23
MutPred		0.21		Loss of helix (P = 0.079);.;.;.;.;
MVP		0.78
MPC		0.36
ClinPred		0.27	T
GERP RS		3.4
Varity_R		0.038
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-74277195;